Thitarodes jiachaensis is a host species of the pathogenic caterpillar fungus Ophiocordyceps sinensis, which is a fungus with broad medical effects and great economic value. Curated genomic information on Thitarodes is still limited, and the interaction between host Thitarodes larvae and O. sinensis during infection is incompletely understood. In this study, we performed transcriptome sequencing for T. jiachaensis before and after O. sinensis infection using the Illumina sequencing platform, and we identified the transcripts associated with the defense response of T. jiachaensis upon O. sinensis infection. A total of 161,804 transcripts and 94,827 unigenes for T. jiachaensis were obtained from 26.62-Gb clean reads, and 35.03% of all the unigenes were annotated in current databases. The expression of 1581 genes was significantly altered following infection; among them, 928 (58.70%) were up-regulated and 653 (41.30%) were down-regulated. Genes encoding physical barriers such as cuticle proteins and peritrophic matrix proteins, antimicrobial peptides (AMPs), pattern recognition receptors (PRRs), and enzymes in the proteolytic cascade were predicted to be involved in the response of T. jiachaensis to O. sinensis infection. Together, these data provide a valuable genomic resource for further studies of Thitarodes and increase our understanding of the host-pathogen interaction that occurs between Thitarodes and O. sinensis. Copyright © 2016 Elsevier B.V. All rights reserved.